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Clinical Practice Osler-Weber-Rendu Syndrome — Dental Implications Contact Author Paulo Sérgio da Silva Santos, DDS, MD; Karin Sá Fernandes, DDS; Marina Helena Magalhães, DDS, PhD Dr. Fernandes Email: [email protected] ABSTRACT Osler-Weber-Rendu syndrome (OWRS) is a rare hereditary, autosomal dominant disease characterized by a local angiodysplasia. Its clinical characteristics are vascular hamarto mas of the skin and oral mucosa, arteriovenous malformations in the lungs, liver, kidney and brain, and episodes of epistaxis. The oral lesions, which become apparent through hemorrhagic telangiectasia, may be the first sign of the disease. This is a case report of a 74-year-old woman whose diagnosis of OWRS was established by her dentist based on the presence of telangiectasia in the skin and oral mucosa, reports of frequent nosebleeds of unknown etiology and a family history of telangiectasia. Amputation of a lower limb and comorbidities, such as cardiopathy, nephropathy and rheumatic disorders, completed the profile. OWRS causes major vascular changes that can be diagnosed initially by a dentist. In this article, we describe the skills and knowledge that dentists need to monitor patients with OWRS properly. For citation purposes, the electronic version is the definitive version of this article: www.cda-adc.ca/jcda/vol-75/issue-7/527.html H ereditary hemorrhagic telangiectasia, or Osler-Weber-Rendu syndrome (OWRS), was first described by Sutton in 1864 and Babington in 1865 as a hereditary epistaxis disease.1,2 In 1896, Rendu described the disease as a pseudo hemophilia related to hereditary epistaxis. In 1901, Osler described the clinical symptoms of the syndrome and emphasized its hereditary occurrence. Weber (1907) recognized OWRS as a clinical entity distinct from hereditary hemophilia, and Hanes (1909) named the syndrome hereditary hemorrhagic telangiectasia. OWRS is an uncommon autosomal dominant disorder characterized by an angiodysplasia in the presence of telangiectasias of the skin and oral mucosa and arteriovenous malformations in the brain, lung, liver and gastrointestinal tract. 3 Its incidence is 1 in 5,000–10,000 in the general population.4 Bleeding episodes may occur due to capillary fragility rather than disturbances in coagulation.1,5 OWRS manifests itself in 2 forms: hereditary hemorrhagic telangiectasia type 1 (HHT1) where there is mutation of the endoglin gene on chromosome 9 with pulmonary involvement; and type 2 (HHT2) with a mutation in the activin receptor-like kinase-1 (ALK-1) gene. HHT2 is the milder form and its onset is later. The proteins produced by the involved genes may play an important role in the integrity of the vessel wall.6 The clinical characteristics of OWRS are epistaxis, telangiectasias of the skin and oral mucosa, visceral lesions (lungs, gastrointes- JCDA • www.cda-adc.ca/jcda • September 2009, Vol. 75, No. 7 • 527 ––– Fernandes ––– During the extraoral and intraoral clinical examination, telangiectasias were found on the skin, especially on the face (Fig. 1) and upper limbs, and were highly visible on the oral mucosa in the regions of the tongue (Fig. 2), hard palate and in the vermilion of the lip. Also present were periodontal disease and caries. Panoramic and periapical radiographs were taken to develop a dental treatment plan. Figure 2: Telangiectasias on the Figure 1: Telangiectasias on the face. The patient’s signs and symptoms tongue. pointed toward a working diagnosis of hereditary hemorrhagic telangiectasia or OWRS. The patient was referred to an Table 1 Results of blood tests internal medicine specialist who conTest Patient’s results Reference value firmed our diagnosis and began medical INR 1 0.7–1.2 monitoring for possible systemic changes resulting from the syndrome. Before aPTT (s) 33 s 30–45 s dental treatment, antibiotic prophylaxis PT (s) 13 s 11–14.6 s (500 mg amoxicillin) was administered BT (min) 2.17 1–4 every 8 hours, starting 12 hours before Platelet count (no./mm3) 280,000 165,000–397,000 the procedure and continuing for 7 days 3 after, to avoid the risk of cerebral abErythrocyte count (cells/mm ) 3.97 4.3–5.9 scesses or pulmonary infections due to Hemoglobin (g/dL) 10.9 12–16 the arteriovenous malformations found aPTT = partial thromboplastin time, BT = bleeding time, INR = international normalized ratio, in OWRS patients.9 Other special measPT = prothrombin time. ures taken during treatment were use of a vertical dental chair position to reduce tinal tract, liver and brain) and family history.7,8 The the risk of lung and nasal bleeding, measurement of differential diagnosis of OWRS includes benign liver blood pressure before and after the procedure, request for disease, benign hereditary telangiectasia, CREST (cal- an up-to-date laboratory evaluation and assessment of cinosis, Raynaud phenomenon, esophageal dysmo- her clinical condition at the time of treatment, because of tility, sclerodactyly and telangiectasia) syndrome and the potential for renal failure and liver disease. ataxia-telangiectasia.8 Dentists can play an important role in the diagnosis Discussion A final diagnosis of OWRS is based on clinical criof OWRS, as its first signs often appear in the oral mu10 cosa. Moreover, the management of a patient with OWRS teria, usually the Curaçao criteria: telangiectasia on must be suited to his or her systemic profile to ensure safe the face, hands and oral cavity; recurrent epistaxis; arteriovenous malformations with visceral involvement; and efficient dental treatment. and family history. Diagnosis is confirmed in the presence of at least 3 of these manifestations.11 In our case, Case Report the clinical signs of telangiectasias of the skin, espeA 74-year-old woman was referred to the special cially in the face, upper limbs and on the oral mucosa, care dentistry centre of our dental school for treatcombined with reported nosebleeds and a family history ment. The patient’s medical history included congestive of telangiectasia and epistaxis were important factors heart failure, chronic renal failure, hypertension, hypo- leading us to suspect OWRS. thyroidism and rheumatism. Her right lower limb had Mucocutaneous telangiectasias occur in about 90% been surgically amputated because of vascular disorders. of cases of OWRS. 8,12 Histologically, they appear as a She reported frequent nosebleeds and a family history of superficial collection of dilated blood vessels with a telangiectasias and epistaxis. layer of endothelial cells in the lamina propria. Electron Laboratory tests showed significant changes in her red microscope studies show a lack of perivascular elastic blood cell count—hypochromic anemia with anisocytosis fibres and smooth muscle.1 and a high level of liver enzymes, with no changes in coOnce the diagnosis is established, complementary imaging tests, such as computed tomography ultrasound agulation (Table 1). 528 JCDA • www.cda-adc.ca/jcda • September 2009, Vol. 75, No. 7 • ––– Osler-Weber-Rendu Syndrome ––– and magnetic resonance imaging, are important to detect whether there is any involvement of organs, such as lungs, liver, kidneys and the brain.10 Pulmonary arteriovenous malformations occur in more than a third of patients with the disease and can cause various complications, such as hypoxia, pulmonary hemorrhage and cerebral embolism.9 Dental professionals must be aware of these complications, keep the dental chair in a vertical position during dental treatment and be prepared to administer oxygen. Vascular lesions in the brain predispose patients to cerebral abscesses,9 a situation that requires special care during invasive dental procedures, such as antibiotic prophylaxis, especially in infected areas. An OWRS patient’s risk of developing a brain abscess ranges from 5% to 9%. Few cases of cerebral abscess due to bacteremia of odontogenic origin have been described so far. Most organisms isolated from brain abscess aspirates have been microaerophilic and anaerobic bacteria commonly and often specifically isolated in periodontal infections.13 Rivero-Garvia14 reported the case of a 41-year-old patient with OWRS who had teeth extracted without antibiotic prophylaxis and, after a few days, developed a brain abscess. This finding confirms the importance of careful dental care in this group of patients. Arteriovenous fistulae in the lungs and vascular malformations are important in the pathogenesis of cerebral abscess. A peripheral septic microembolism can reach the brain and cause a brain abscess. Approximately 10% of patients with arteriovenous fistulae in the lungs develop cerebral abscess.15,16 There is no evidence in the scientific literature of the need to use antibiotic prophylaxis in invasive dental procedures that may cause bacteremia in patients with arteriovenous malformations, who have a higher likelihood of developing cerebral abscesses. 2 However, the rarity of the disease and lack of prospective studies addressing the risk of brain abscesses through oral manipulation makes the use of antibiotic prophylaxis empirical in this case. Although for normal patients there is little risk of exacerbation of anemia due to dental treatment, patients with OWRS with severe anemia (hemoglobin level <10 mg/dL) should avoid certain routine procedures, as invasive procedures can exacerbate anemia, depending on the amount of blood that is lost.17,18 The medical treatment of OWRS is only palliative and depends on the severity and stage of disease. Symptoms of OWRS increase with age. Some measures, including iron supplements, blood transfusions and laser therapy, have met with varying degrees of success; sclerosing techniques have been used to control epistaxis. In patients with recurrent episodes of epistaxis, surgery of the nasal septum may be indicated.12 A study in Italy19 reported excellent hemostatic results using Nd-Yag laser treatment in 8 patients with OWRS for the control of epistaxis and oral bleeding. This treatment was well accepted by patients and costs were low. However, researchers are divided on the efficiency of the use of lasers with OWRS patients, and there is no specific protocol for their use. The prognosis associated with OWRS is good, but the morbidity is significant.20 Moreover, a mortality rate of 1%–2% is reported due to complications related to epistaxis, and it rises to 10% in patients with cerebral abscess.6 OWRS causes major vascular changes that may be initially diagnosed by the dentist. Skill and knowledge of the disease are required for proper dental monitoring of patients with OWRS. a THE AUTHORS Dr. Silva Santos is a post-graduate student in the department of oral pathology, School of Dentistry, University of São Paulo, São Paulo, Brazil. Dr. Fernandes is a post-graduate student in the department of oral pathology, School of Dentistry, University of São Paulo, São Paulo, Brazil. Dr. Magalhães is professor and chair of the department of oral pathology, School of Dentistry, University of São Paulo, São Paulo, Brazil. Correspondence to: Dr. Karin Sá Fernandes, Av. Prof. Lineu Prestes, 2227, São Paulo SP, Brazil 05508-000. The authors have no declared financial interests. This article has been peer reviewed. References 1. Bartolucci EG, Swan RH, Hurt WC. Oral manifestations of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease). Review and case reports. J Periodontol. 1982;53(3):163-7. 2. te Veldhuis EC, te Veldhuis AH, van Dijk FS, Kwee ML, van Hagen JM, Baart JA, et al. Rendu-Osler-Weber disease: update of medical and dental considerations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;105(2):e38-41. 3. Letteboer TG, Zewald RA, Kamping EJ, de Haas G, Mager JJ, Snijder RJ, et al. Hereditary hemorrhagic telangiectasia: ENG and ALK-1 mutations in Dutch patients. Hum Genet. 2005;116(1-2):8-16. Epub 2004 Oct 23. 4. Begbie ME, Wallace GM, Shovlin CL. Hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): a view from the 21st century. Postgrad Med J. 2003;79(927):18-24. 5. Burket LW, Alderman MM, Beideman RW, Brightman VJ, Greenberg MS, Hamner JE, et al. Hemorrhage and hemorrhagic lesions. In: Lynch MA, editor. Burket’s oral medicine. 7th ed. Philadelphia: JB Lippincott; 1977. p. 100-14. 6. Neville BW, Damm DD, Allen CM, Bouquet JE. Dermatologic diseases. In: Oral and maxillofacial pathology. 2th ed. Philadelphia: Saunders; 2004. p. 627-9. 7. Dakeishi M, Shioya T, Wada Y, Shindo T, Otaka K, Manabe M, et al. Genetic epidemiolology of hereditary hemorrhagic telangiectasia in a local community in the northern part of Japan. Hum Mutat. 2002;19(2):140-8. JCDA • www.cda-adc.ca/jcda • September 2009, Vol. 75, No. 7 • 529 ––– Fernandes ––– 8. Sadick H, Sadick M, Götte K, Naim R, Riedel F, Bran G, et al. Hereditary hemorrhagic telangiectasia: an update on clinical manifestations and diagnostic measures. Wien Klin Wochenschr. 2006;118(3-4):72-80. 9. Tabakow P, Jarmundowicz W, Czapiga B, Czapiga E. Brain abscess as the first clinical manifestation of multiple pulmonary arteriovenous malformations in a patient with hereditary hemorrhagic telangiectasia (Rendu-OslerWeber disease). Folia Neuropathol. 2005;43(1):41-4. 10. Daina E, D’Ovidio F, Sabbà C. Introduction: hereditary hemorrhagic telangiectasia as a rare disease. Curr Pharm Des. 2006;12(10):1171-2. 11. Fuchizaki U, Miyamori H, Kitagawa S, Kaneko S, Kobayashi K. Hereditary haemorrhagic telangiectasia (Rendu-Osler-Weber disease). Lancet. 2003;362(9394):1490-4. 12. Folz BJ, Lippert BM, Wollstein AC, Tennie J, Happle R, Werner JA. Mucocutaneous telangiectases of the head and neck in individuals with hereditary hemorrhagic telangiectasia — analysis of distribution and symptoms. Eur J Dermatol. 2004;14(6):407-11. 13. Sell B, Evans J, Horn D. Brain abscess and hereditary hemorrhagic telangiectasia. South Med J. 2008;101(6):618-25. 15. Shovlin C, Bamford K, Wray D. Post-NICE 2008: antibiotic prophylaxis prior to dental procedures for patients with pulmonary arteriovenous malformations (PAVMs) and hereditary haemorrhagic telangiectasia. Br Dent J. 2008;205(10):531-3. 16. Shovlin CL, Jackson JE, Bamford KB, Jenkins IH, Benjamin AR, Ramadan H, et al. Primary determinants of ischemic stroke/brain abscess risks are independent of severity of pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia. Thorax. 2008;63(3):259-66. Epub 2007 Nov 2. 17. Derossi SS, Raghavendra S. Anemia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;95(2):131-41. 18. Glick M. Medical considerations for dental practice: an interactive CDROM. Hanover Park, Ill: Quintessence; 2005. 19. Galletta A, Amato G. [Hereditary hemorrhagic telangiectasia (OslerRendu-Weber disease) management of epistaxis and oral hemorrhage by Nd-Yag laser]. Minerva Stomatol. 1998;47(6):283-6. [Italian] 20. McDonald MJ, Brophy BP, Kneebone C. Rendu-Osler-Weber syndrome: a current perspective on cerebral manifestations. J Clin Neurosci. 1998;5(3):345-50. 14. Rivero-Garvia M, Boto GR, Perez-Zamarron A, Alonso-Lera P, Zimman H, Saldana CJ. [Cerebral abscess associated to Rendu-Osler-Weber disease]. Rev Neurol. 2006;43(5):311-2. [Spanish] 530 JCDA • www.cda-adc.ca/jcda • September 2009, Vol. 75, No. 7 •